Background: In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA).
Objective: We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat.
Methods: Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels.
Results: In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50.
Conclusions: During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible.
{"title":"Omalizumab reduces anaphylactic reactions and allows food introduction in food-allergic in children with severe asthma: An observational study.","authors":"Stefania Arasi, Arianna Cafarotti, Francesca Galletta, Valentina Panetta, Carla Riccardi, Veronica Calandrelli, Vincenzo Fierro, Lamia Dahdah, Maria Cristina Artesani, Rocco Luigi Valluzzi, Valentina Pecora, Valeria Tallarico, Giulio Dinardo, Lucia Lo Scalzo, Alessandro Fiocchi","doi":"10.1111/all.16314","DOIUrl":"https://doi.org/10.1111/all.16314","url":null,"abstract":"<p><strong>Background: </strong>In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA).</p><p><strong>Objective: </strong>We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat.</p><p><strong>Methods: </strong>Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels.</p><p><strong>Results: </strong>In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50.</p><p><strong>Conclusions: </strong>During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov, NCT06316414.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anouk von Borstel, Simone Reinwald, Pei M. Aui, Craig I. McKenzie, Nirupama Varese, P. Mark Hogarth, Mark Hew, Robyn E. O'Hehir, Menno C. van Zelm
{"title":"Expansion of phenotypically modified type 2 memory B cells after allergen immunotherapy","authors":"Anouk von Borstel, Simone Reinwald, Pei M. Aui, Craig I. McKenzie, Nirupama Varese, P. Mark Hogarth, Mark Hew, Robyn E. O'Hehir, Menno C. van Zelm","doi":"10.1111/all.16320","DOIUrl":"https://doi.org/10.1111/all.16320","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Casper E. W. Gijsen, Thijs R. P. Bogers, Jean W. M. Muris, Marieke W. P. van van Horck, Edward Dompeling
{"title":"Letter to the editor: Efficacy of eHealth monitoring in pediatric asthma","authors":"Casper E. W. Gijsen, Thijs R. P. Bogers, Jean W. M. Muris, Marieke W. P. van van Horck, Edward Dompeling","doi":"10.1111/all.16317","DOIUrl":"https://doi.org/10.1111/all.16317","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alisa Landgraf, Sascha Hein, Kathrin Elisabeth Paulus‐Tremel, Michelle Beatrice Wolff, Meike Arend, Ann‐Christine Junker, Daniel Strecker, Sascha Döring, Elke Völker, Thomas Holzhauser, Sandra Schmidt, Susanne Kaul, Stefan Schülke, Vera Mahler
{"title":"Establishment of an ELISA‐based in vitro test system to quantify the major honey bee venom allergen Api m 10 in crude bee venoms and therapy allergen products","authors":"Alisa Landgraf, Sascha Hein, Kathrin Elisabeth Paulus‐Tremel, Michelle Beatrice Wolff, Meike Arend, Ann‐Christine Junker, Daniel Strecker, Sascha Döring, Elke Völker, Thomas Holzhauser, Sandra Schmidt, Susanne Kaul, Stefan Schülke, Vera Mahler","doi":"10.1111/all.16313","DOIUrl":"https://doi.org/10.1111/all.16313","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kymble Spriggs, Elizabeth Leahy, Nicole Weibel, Sara Barnes
{"title":"Effect of venom immunotherapy and sting challenge on HRQoL measured by venom‐allergy quality of life questionnaire (VQLQ) in Jack jumper ant allergic patients","authors":"Kymble Spriggs, Elizabeth Leahy, Nicole Weibel, Sara Barnes","doi":"10.1111/all.16319","DOIUrl":"https://doi.org/10.1111/all.16319","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Grace Hren, Ester Del Duca, Helen He, Andrew L. Ji, Emma Guttman‐Yassky
{"title":"Algorithms in allergy: Diagnosis and management of atopic dermatitis in adulthood","authors":"M. Grace Hren, Ester Del Duca, Helen He, Andrew L. Ji, Emma Guttman‐Yassky","doi":"10.1111/all.16315","DOIUrl":"https://doi.org/10.1111/all.16315","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C L Lai, B Santner-Nanan, P J Maltese, C K S Ong, D J Palmer, D E Campbell, M Makrides, M Gold, R Nanan, S L Prescott, P S Hsu
Background: Reasons for Th2 skewing in IgE-mediated food allergies remains unclear. Clinical observations suggest impaired T cell activation may drive Th2 responses evidenced by increased atopic manifestations in liver transplant patients on tacrolimus (a calcineurin inhibitor). We aimed to assess differentiation potential, T cell activation and calcium influx of naïve CD4+ T cells in children with IgE-mediated food allergies.
Methods: Peripheral blood mononuclear cells from infants in the Starting Time for Egg Protein (STEP) Trial were analyzed by flow cytometry to assess Th1/Th2/Treg development. Naïve CD4+ T cells from children with and without food allergies were stimulated for 7 days to assess Th1/Th2/Treg transcriptional factors and cytokines. Store operated calcium entry (SOCE) was measured in children with and without food allergies. The effect of tacrolimus on CD4+ T cell differentiation was assessed by treating stimulated naïve CD4+ T cells from healthy volunteers with tacrolimus for 7 days.
Results: Egg allergic infants had impaired development of IFNγ+ Th1 cells and FoxP3+ transitional CD4+ T cells compared with non-allergic infants. This parallels reduced T-bet, IFNγ and FoxP3 expression in naïve CD4+ T cells from food allergic children after in vitro culture. SOCE of naïve CD4+ T cells was impaired in food allergic children. Naïve CD4+ T cells treated with tacrolimus had reduced IFNγ, T-bet, and FoxP3, but preserved IL-4 expression.
Conclusions: In children with IgE-mediated food allergies, dysregulation of T helper cell development is associated with impaired SOCE, which underlies an intrinsic impairment in Th1 and Treg differentiation. Along with tacrolimus-induced Th2 skewing, this highlights an important role of SOCE/calcineurin pathway in T helper cell differentiation.
背景:IgE 介导的食物过敏中 Th2 偏倚的原因仍不清楚。临床观察表明,T细胞活化受损可能会驱动Th2反应,服用他克莫司(一种钙神经蛋白抑制剂)的肝移植患者特应性表现增加就是证明。我们的目的是评估 IgE 介导的食物过敏患儿的分化潜能、T 细胞活化和幼稚 CD4+ T 细胞的钙离子流入:流式细胞术分析了鸡蛋蛋白起始时间(STEP)试验中婴儿的外周血单核细胞,以评估Th1/Th2/Treg的发育情况。对患有和未患有食物过敏症儿童的新生 CD4+ T 细胞进行为期 7 天的刺激,以评估 Th1/Th2/Treg 转录因子和细胞因子。对食物过敏儿童和非食物过敏儿童的储存操作钙离子通道(SOCE)进行了测量。用他克莫司刺激健康志愿者的幼稚 CD4+ T 细胞 7 天,评估他克莫司对 CD4+ T 细胞分化的影响:结果:与不过敏的婴儿相比,对鸡蛋过敏的婴儿的 IFNγ+ Th1 细胞和 FoxP3+ 过渡性 CD4+ T 细胞发育受损。这与体外培养后食物过敏儿童的幼稚 CD4+ T 细胞中 T-bet、IFNγ 和 FoxP3 表达减少的情况相似。食物过敏儿童的幼稚 CD4+ T 细胞的 SOCE 功能受损。用他克莫司处理的幼稚CD4+ T细胞的IFNγ、T-bet和FoxP3表达量减少,但IL-4表达量保持不变:结论:在IgE介导的食物过敏患儿中,T辅助细胞发育失调与SOCE受损有关,而SOCE受损是Th1和Treg分化内在障碍的基础。这与他克莫司诱导的Th2倾斜一起,凸显了SOCE/钙神经蛋白通路在T辅助细胞分化中的重要作用。
{"title":"Impaired calcium influx underlies skewed T helper cell differentiation in children with IgE-mediated food allergies.","authors":"C L Lai, B Santner-Nanan, P J Maltese, C K S Ong, D J Palmer, D E Campbell, M Makrides, M Gold, R Nanan, S L Prescott, P S Hsu","doi":"10.1111/all.16310","DOIUrl":"https://doi.org/10.1111/all.16310","url":null,"abstract":"<p><strong>Background: </strong>Reasons for Th2 skewing in IgE-mediated food allergies remains unclear. Clinical observations suggest impaired T cell activation may drive Th2 responses evidenced by increased atopic manifestations in liver transplant patients on tacrolimus (a calcineurin inhibitor). We aimed to assess differentiation potential, T cell activation and calcium influx of naïve CD4<sup>+</sup> T cells in children with IgE-mediated food allergies.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells from infants in the Starting Time for Egg Protein (STEP) Trial were analyzed by flow cytometry to assess Th1/Th2/Treg development. Naïve CD4<sup>+</sup> T cells from children with and without food allergies were stimulated for 7 days to assess Th1/Th2/Treg transcriptional factors and cytokines. Store operated calcium entry (SOCE) was measured in children with and without food allergies. The effect of tacrolimus on CD4<sup>+</sup> T cell differentiation was assessed by treating stimulated naïve CD4<sup>+</sup> T cells from healthy volunteers with tacrolimus for 7 days.</p><p><strong>Results: </strong>Egg allergic infants had impaired development of IFNγ<sup>+</sup> Th1 cells and FoxP3<sup>+</sup> transitional CD4<sup>+</sup> T cells compared with non-allergic infants. This parallels reduced T-bet, IFNγ and FoxP3 expression in naïve CD4<sup>+</sup> T cells from food allergic children after in vitro culture. SOCE of naïve CD4<sup>+</sup> T cells was impaired in food allergic children. Naïve CD4<sup>+</sup> T cells treated with tacrolimus had reduced IFNγ, T-bet, and FoxP3, but preserved IL-4 expression.</p><p><strong>Conclusions: </strong>In children with IgE-mediated food allergies, dysregulation of T helper cell development is associated with impaired SOCE, which underlies an intrinsic impairment in Th1 and Treg differentiation. Along with tacrolimus-induced Th2 skewing, this highlights an important role of SOCE/calcineurin pathway in T helper cell differentiation.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Horace Rhee, Lindsay M Henderson, Rebecca N Bauer, Kit Wong, Tracy L Staton, David F Choy, Prajna Banerjee, Victor Poon, Kenta Yoshida, Chen Chen, Keyi Long, Gizette Sperinde, Steven T Laing, Nicholas S Jones, Sara B Glickstein, Parul Dayal, Alice Fong, Ajit Dash, Grazyna Pulka, Brian Leaker, Dave Singh, Peter Bradding
Background: Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti-tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract.
Methods: Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks. The primary endpoint was time to the first composite exacerbation event. Phase 1c patients (n = 27) received one intravenous dose of 300 or 1800 mg MTPS9579A or placebo. Both trials measured MTPS9579A concentrations and effects on tryptase in serum and nasal lining fluid; phase 1c also analyzed bronchial lining fluid.
Results: MTPS9579A did not meet the primary endpoint (hazard ratio = 0.90; 95% CI: 0.55-1.47; p = 0.6835); exacerbation rates in the placebo group were low. Serum and nasal MTPS9579A pharmacokinetics and tryptase levels were consistent with data from healthy volunteers. However, in phase 1c patients, compared to nasal levels, MTPS9579A bronchial concentrations were 6.8-fold lower, and bronchial active and total tryptase levels were higher (119-fold and 30-fold, respectively). Pharmacokinetic/pharmacodynamic modeling predicted intravenous doses of 3800 mg every 4 weeks would be necessary to achieve 95% active tryptase inhibition from baseline.
Conclusions: The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy.
{"title":"Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor MTPS9579A in asthma.","authors":"Horace Rhee, Lindsay M Henderson, Rebecca N Bauer, Kit Wong, Tracy L Staton, David F Choy, Prajna Banerjee, Victor Poon, Kenta Yoshida, Chen Chen, Keyi Long, Gizette Sperinde, Steven T Laing, Nicholas S Jones, Sara B Glickstein, Parul Dayal, Alice Fong, Ajit Dash, Grazyna Pulka, Brian Leaker, Dave Singh, Peter Bradding","doi":"10.1111/all.16309","DOIUrl":"https://doi.org/10.1111/all.16309","url":null,"abstract":"<p><strong>Background: </strong>Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti-tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract.</p><p><strong>Methods: </strong>Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks. The primary endpoint was time to the first composite exacerbation event. Phase 1c patients (n = 27) received one intravenous dose of 300 or 1800 mg MTPS9579A or placebo. Both trials measured MTPS9579A concentrations and effects on tryptase in serum and nasal lining fluid; phase 1c also analyzed bronchial lining fluid.</p><p><strong>Results: </strong>MTPS9579A did not meet the primary endpoint (hazard ratio = 0.90; 95% CI: 0.55-1.47; p = 0.6835); exacerbation rates in the placebo group were low. Serum and nasal MTPS9579A pharmacokinetics and tryptase levels were consistent with data from healthy volunteers. However, in phase 1c patients, compared to nasal levels, MTPS9579A bronchial concentrations were 6.8-fold lower, and bronchial active and total tryptase levels were higher (119-fold and 30-fold, respectively). Pharmacokinetic/pharmacodynamic modeling predicted intravenous doses of 3800 mg every 4 weeks would be necessary to achieve 95% active tryptase inhibition from baseline.</p><p><strong>Conclusions: </strong>The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hana Seastedt, Xiaorui Han, Andrea Fernandes, Stephen J Galli, Scott D Boyd, Kari C Nadeau, Monali Manohar, Sharon Chinthrajah
{"title":"Association of cytotoxic effector memory CD8<sup>+</sup> T cells with sustained unresponsiveness after peanut oral immunotherapy.","authors":"Hana Seastedt, Xiaorui Han, Andrea Fernandes, Stephen J Galli, Scott D Boyd, Kari C Nadeau, Monali Manohar, Sharon Chinthrajah","doi":"10.1111/all.16307","DOIUrl":"https://doi.org/10.1111/all.16307","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}